Disposition of perfluorinated acid isomers in Sprague-Dawley rats; part 1: single dose.
Perfluorinated acids (PFAs) and their precursors (PFA-precursors) exist in the environment as linear and multiple branched isomers. These isomers are hypothesized to have different biological properties, but no isomer-specific data are currently available. The present study is the first in a two-part project examining PFA isomer-specific uptake, tissue distribution, and elimination in a rodent model. Seven male Sprague-Dawley rats were administered a single gavage dose of approximately 500 microg/kg body weight perfluorooctane sulfonate (C(8)F(17)SO(3)(-), PFOS), perfluorooctanoic acid (C(7)F(15)CO(2)H, PFOA), and perfluorononanoic acid (C(8)F(17)CO(2)H, PFNA) and 30 microg/kg body weight perfluorohexane sulfonate (C(6)F(13)SO(3)(-), PFHxS). Over the subsequent 38 d, urine, feces, and tail-vein blood samples were collected intermittently, while larger blood volumes and tissues were collected on days 3 and 38 for isomer analysis by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). For all PFAs, branched isomers generally had lower blood depuration half-lives than the corresponding linear isomer. The most remarkable exception was for the PFOS isomer containing an alpha-perfluoromethyl branch (1m-PFOS), which was threefold more persistent than linear PFOS, possibly due to steric shielding of the hydrophilic sulfonate moiety. For perfluoromonomethyl-branched isomers of PFOS, a structure-property relationship was observed whereby branching toward the sulfonate end of the perfluoroalkyl chain resulted in increased half-lives. For PFHxS, PFOA, and PFOS, preferential elimination of branched isomers occurred primarily via urine, whereas for PFNA preferential elimination of the isopropyl isomer occurred via both urine and feces. Changes in the blood isomer profiles over time and their inverse correlation to isomer elimination patterns in urine, feces, or both provided unequivocal evidence of significant isomer-specific biological handling. Source assignment based on PFA isomer profiles in biota must therefore be conducted with caution, because isomer profiles are unlikely to be conserved in biological samples.
Benskin
Jonathan P
JP
Division of Analytical and Environmental Toxicology, Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alverta, Canada.
De Silva
Amila O
AO
Martin
Leah J
LJ
Arsenault
Gilles
G
McCrindle
Robert
R
Riddell
Nicole
N
Mabury
Scott A
SA
Martin
Jonathan W
JW
D000818:Animals; D004785:Environmental Pollutants / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D005243:Feces / Q000737:chemistry; D006845:Hydrocarbons, Fluorinated / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D007536:Isomerism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D004785:Environmental Pollutants; D006845:Hydrocarbons, Fluorinated